The impact of prenatal maternal-fetal metal levels and placental transfer efficiency of metals on neonatal thyroid function: The modulatory role of maternal vitamin D levels in pregnancy

Prenatal metal exposure can disrupt the homeostasis of foetal thyroid function. Drawing on data from 2,444 mother-child pairs involved in Ma'anshan birth cohort (MABC) study, we explored the associations of prenatal fourteen metals [arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), thallium (Tl), zinc (Zn), selenium (Se), vanadium (V), cobalt (Co), barium (Ba), molybdenum (Mo), iron (Fe), copper (Cu)] exposure and placental transfer efficiency (PTE) of these metals with thyroid function in newborns by analysing three types of biological samples. We calculated the PTE of metals and performed statistical analysis using multiple linear regression, and weighted quantile sum (WQS),interaction and marginal effects models. Results indicated that the PTE of metals (As, Hg, Mn, Zn, Se, Co, Cu and Fe), maternal Cd, and cord metals (As, Mn, Zn, Se, Co, Cu, and Fe) were positively associated with neonatal thyroid-stimulating hormone (TSH) levelsin the adjusted model. The PTE of metals (Mn, Cu, and Fe), maternal Tl, cord metals (Mn, Cu, and Fe) were negatively associated with neonatal free thyroxine (FT₄) levels. The WQS of the metal mixture, measured in both maternal blood and cord blood, as well as the PTE of metals, demonstrated a significant inverse association with FT₄. Among these, maternal Tl and As, cord Cu, and the PTE of Cu made the most substantial contributions to these associations. Potential interactions between maternal vitamin D levels and some metals (PTE of Hg and Fe, maternal Hg, Mn and Fe, cord Tl and Ba) on neonatal TSH and FT₄ were observed. Notably, Hg and Fe exposure were almost significantly associated with neonatal TSH and FT₄ only in the group with maternal vitamin D deficiency.This study reveals that both single and mixed exposures to multiple metals during the prenatal period may affect the thyroid function of the fetus in utero, and highlights the potential key role of the relatively high metal transport efficiency between the mother and the fetus.